HypertensionPhase 2NCT01297335

Effect of Intrathecal Clonidine in Hypertensive Subjects With Poorly Controlled Blood Pressure

A Phase 2 study testing clonidine in people with Hypertension, run by The Center for Clinical Research, Winston-Salem, NC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine the acute efficacy of intrathecal clonidine to reduce blood pressure in hypertensive subjects with poor blood pressure control and describe its effects on cardiovascular function. Read more about this study

Who is it for?: Ages 30 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Hypertension
What is being tested?: clonidine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: No sites listed yet
Study dates: Feb 2011to Jul 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 30 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Diagnosis of Hypertension
Stable systolic blood pressure >140 mmHg and < 190 mmHg
On 3 or more antihypertensive medications
On a diuretic
Patients must be able to understand the risks

Who cannot join

Allergy to clonidine
Presently on clonidine orally or transdermally
Known or suspected correctable causes of secondary hypertension
Breast Feeding or Pregnant women
Unstable Ischemic Heart Disease
Unstable Angina

Show all 28Show fewer

Intracoronary Stent Placement
Coronary bypass within last 6 months
Myocardial Infarction within last 6 months
Congestive Failure
Cardiac Arrhythmias
Known Cerebral Vascular Disease
Renal Disease
Evidence of Injection Site Infection
Known Bleeding Disorders
Hepatic Insufficiency
Renal Insufficiency
Participation in an investigational drug study within 30 day of enrollment
Prohibited Medications:
Clonidine
Yohimbine
Tricyclic Antidepressants
Mirtazapine
Digitalis
Reserpine
Guanethidine
Non-Steroidal Anti-inflammatory Medication
Alcohol or Barbiturates within 48 hours of study procedure

About this study

Official title: Hemodynamic Effect of Intrathecal Clonidine in Hypertensive Subjects: A Pilot Study to Assess Its Effectiveness in Hypertensive Subjects With Poor Blood Pressure Control (Phase II)

Read the detailed description

Hypertension occurs commonly, is associated with major morbidity and mortality, and responds poorly to current therapies in a small minority of compliant patients. The goal of this investigator-initiated study is to determine whether intrathecal administration of clonidine reduces blood pressure in hypertensive patients, focusing on a group who often achieve inadequate blood pressure control with multiple drug therapy.

After consent, pts will be screened and if qualified brought into center and intrathecal injection of clonidine given. Patients will be closely monitored for 4 hours, while data is collected.

Conditions: Hypertension
Being tested: clonidine
Keywords: intrathecal, clonidine, poorly, controlled, hypertension
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

clonidineDrug
Also called catapres
Intrathecal Clonidine

Study groups in NCT01297335
Study group	Role	What they receive
Intrathecal Clonidine	Experimental	Subject will receive one time Clonidine injection via lower lumber interspace. Clonidine (Duraclon), 100 μg/ml, 1.5 ml will be diluted to 2 ml with preservative free saline, and total of 150 μg will be delivered. Supine and sitting blood pressures and heart rate will be measured at 10 minute intervals until 60 minutes after clonidine administration, then at 15 minutes for next 3 hours. Receives: Drug: clonidine

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Blood Pressure After Intrathecal Injection of Clonidine.
Subjects baseline blood pressure (systolic blood pressure (SBP), and diastolic blood pressure (DBP)), and blood pressures after clonidine injection was compared against baseline to assess efficacy of clonidine in refractory hypertensive subjects. Subject's blood pressure was monitored continuously after intrathecal injection of clonidine until subjects blood pressure nadir and return to pre clonidine injection level. The mean value reported below are the average changes in blood pressure from baseline (pre clonidine injection) in both SBP and DBP during post clonidine injection blood pressure monitoring for 4 hours.
Blood pressure measurements were collected every 10 minutes for first hour after injection, and every 15 minutes after the first hour, up to 4 hours were averaged to report the change from baseline.
Measured: Baseline, Every 10 Minutes for first hour after clonidine injection, and every 15 minutes after first hour, until 4 hours after clonidine injection

Secondary outcomes (2)

Likert Scale Pain Rating
Likert scale is 11 point digital pain rating system that asks subjects to rate their pain from 0 to 10. Rating of 0 means no pain at all, and in increasing order, 10 would mean worst pain imaginable/ unbearable pain.
Measured: Pre-dose and 1 hour post injection.
Changes in Visual Analogue Scale (VAS) Ratings of Sedation and Sensation of Dry Mouth Reported by the Subjects, Pre and 1 Hour Post Injection
Subjects were asked to rate severity of two of the most common side effects of clonidine, sedation and sensation of dry mouth, at pre and post (1 hour after) intrathecal administration of clonidine. The mean changes between pre and post injection VAS ratings of sedation and sensation of dry mouth are reported below. The VAS scale ranges from 1 to 10 cm, with higher values indicating higher level of sedation and higher level of dry mouth.
Measured: Before clonidine injection (Baseline), and at 1 hour after clonidine injection.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2011Jul 2012

First posted16 Feb 2011 (estimated)
Study startFeb 2011
Primary completionJul 2012
Study completionJul 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (54)Papers the sponsor has linked to this study.
Other trials for HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01297335
Sponsor's protocol ID: 1461 Clonidine
Other IDs: 1461
Status last verified: Sep 2016
First submitted: 14 Feb 2011
Last updated: 19 Oct 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No: no individual's data will be shared with anyone other than the members of the study staff, and the confidentiality will be maintained in accordance with HIPAA rules.

Publications

Onesti G, Schwartz AB, Kim KE, Swartz C, Brest AN. Pharmacodynamic effects of a new antihypertensive drug, Catapres (ST-155). Circulation. 1969 Feb;39(2):219-28. doi: 10.1161/01.cir.39.2.219. No abstract available.
PubMed 4884576
Davies DS, Wing AM, Reid JL, Neill DM, Tippett P, Dollery CT. Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine. Clin Pharmacol Ther. 1977 May;21(5):593-601. doi: 10.1002/cpt1977215593.
PubMed 870272
Frisk-Holmberg M, Paalzow L, Wibell L. Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension. Demonstration of a therapeutic window in man. Eur J Clin Pharmacol. 1984;26(3):309-13. doi: 10.1007/BF00548760.
PubMed 6734692
Reid JL, Wing LM, Mathias CJ, Frankel HL, Neill E. The central hypotensive effect of clonidine. Studies in tetraplegic subjects. Clin Pharmacol Ther. 1977 Apr;21(4):375-81. doi: 10.1002/cpt1977214375.
PubMed 321174
Brown MJ, Struthers AD, di Silvio L. Peripheral alpha 2 adrenoceptor stimulation contributes to the sympatholytic effect of guanfacine in humans. J Cardiovasc Pharmacol. 1985;7 Suppl 6:S159-61. doi: 10.1097/00005344-198500076-00027.
PubMed 2414580
Guthrie GP Jr, Kotchen TA. Effects of prazosin and clonidine on sympathetic and baroreflex function in patients with essential hypertension. J Clin Pharmacol. 1983 Aug-Sep;23(8-9):348-54. doi: 10.1002/j.1552-4604.1983.tb02747.x.
PubMed 6630584
Mohanty PK, Sowers JR, McNamara C, Thames MD. Reflex vasoconstrictor responses to cardiopulmonary baroreceptor unloading, head-up tilt, and cold pressor testing in elderly mild-to-moderate hypertensives: effect of clonidine. J Cardiovasc Pharmacol. 1987;10 Suppl 12:S135-7.
PubMed 2455165
Muzi M, Goff DR, Kampine JP, Roerig DL, Ebert TJ. Clonidine reduces sympathetic activity but maintains baroreflex responses in normotensive humans. Anesthesiology. 1992 Nov;77(5):864-71. doi: 10.1097/00000542-199211000-00005.
PubMed 1443738
Houston MC. Treatment of hypertensive emergencies and urgencies with oral clonidine loading and titration. A review. Arch Intern Med. 1986 Mar;146(3):586-9.
PubMed 3513726
Masotti G, Scarti L, Poggesi L, Bisi G, Gallini C, Neri Serneri GG. Changes in cardiac function after effective treatment of hypertensive emergencies with i.v. clonidine. Eur Heart J. 1984 Dec;5(12):1036-42. doi: 10.1093/oxfordjournals.eurheartj.a061605.
PubMed 6534750
Niarchos AP. Evaluation of intravenous clonidine in hypertensive emergencies. J Clin Pharmacol. 1978 Apr;18(4):220-8. doi: 10.1002/j.1552-4604.1978.tb01596.x.
PubMed 632367
Magorien RD, Hermiller JB, Unverferth DV, Leier CV. Regional hemodynamic effects of clonidine in congestive heart failure. J Cardiovasc Pharmacol. 1985 Jan-Feb;7(1):91-6. doi: 10.1097/00005344-198501000-00015.
PubMed 2580157
Zochowski RJ, Lada W. Intravenous clonidine treatment in acute myocardial infarction (with comparison to a nitroglycerin-treated and control group). J Cardiovasc Pharmacol. 1986;8 Suppl 3:S41-5.
PubMed 2429112
Wallace AW, Galindez D, Salahieh A, Layug EL, Lazo EA, Haratonik KA, Boisvert DM, Kardatzke D. Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery. Anesthesiology. 2004 Aug;101(2):284-93. doi: 10.1097/00000542-200408000-00007.
PubMed 15277909
Byrd BF 3rd, Collins HW, Primm RK. Risk factors for severe bradycardia during oral clonidine therapy for hypertension. Arch Intern Med. 1988 Mar;148(3):729-33.
PubMed 3341873

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Hemodynamic Effect of Intrathecal Clonidine in Hypertensive Subjects: A Pilot Study to Assess Its Effectiveness in Hypertensive Subjects With Poor Blood Pressure Control (Phase II)
ClinicalTrials.gov ID: NCT01297335
Acronym / sponsor ID: 1461 Clonidine
Conditions: Hypertension
Keywords: intrathecal, clonidine, poorly, controlled, hypertension
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 10 participants (actual)
Lead sponsor: The Center for Clinical Research, Winston-Salem, NCUniversity, hospital or other
Collaborators: Medtronic
Study start: Feb 2011
Primary completion: Jul 2012 (actual)
Study completion: Jul 2012 (actual)
First posted: 16 Feb 2011 (estimated)
Results: Posted 1 Jan 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

After consent, pts will be screened and if qualified brought into center and intrathecal injection of clonidine given. Patients will be closely monitored for 4 hours, while data is collected.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Intrathecal Clonidine	Experimental	Drug: clonidineSubject will receive one time Clonidine injection via lower lumber interspace. Clonidine (Duraclon), 100 μg/ml, 1.5 ml will be diluted to 2 ml with preservative free saline, and total of 150 μg will be delivered. Supine and sitting blood pressures and heart rate will be measured at 10 minute intervals until 60 minutes after clonidine administration, then at 15 minutes for next 3 hours.

Who may qualify

Ages: 30 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Diagnosis of Hypertension
Stable systolic blood pressure >140 mmHg and < 190 mmHg
On 3 or more antihypertensive medications
On a diuretic
Patients must be able to understand the risks

Key exclusion criteria (28 listed)

Allergy to clonidine
Presently on clonidine orally or transdermally
Known or suspected correctable causes of secondary hypertension
Breast Feeding or Pregnant women
Unstable Ischemic Heart Disease

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
clonidineAlso: catapresIntrathecal Clonidine	Drug	Intrathecal Clonidine

Primary outcome

Change in Blood Pressure After Intrathecal Injection of Clonidine.
Time frame: Baseline, Every 10 Minutes for first hour after clonidine injection, and every 15 minutes after first hour, until 4 hours after clonidine injection
Subjects baseline blood pressure (systolic blood pressure (SBP), and diastolic blood pressure (DBP)), and blood pressures after clonidine injection was compared against baseline to assess efficacy of clonidine in refractory hypertensive subjects. Subject's blood pressure was monitored continuously after intrathecal injection of clonidine until subjects blood pressure nadir and return to pre clonidine injection level. The mean value reported below are the average changes in blood pressure from baseline (pre clonidine injection) in both SBP and DBP during post clonidine injection blood pressure monitoring for 4 hours. Blood pressure measurements were collected every 10 minutes for first hour after injection, and every 15 minutes after the first hour, up to 4 hours were averaged to report the change from baseline.

2 secondary outcomes

Likert Scale Pain Rating
Time frame: Pre-dose and 1 hour post injection.
Changes in Visual Analogue Scale (VAS) Ratings of Sedation and Sensation of Dry Mouth Reported by the Subjects, Pre and 1 Hour Post Injection
Time frame: Before clonidine injection (Baseline), and at 1 hour after clonidine injection.

Results and safety

Results posted to the registry on 1 Jan 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Intrathecal Clonidine	10	10

Primary outcome: Change in Blood Pressure After Intrathecal Injection of Clonidine.

Time frame: Baseline, Every 10 Minutes for first hour after clonidine injection, and every 15 minutes after first hour, until 4 hours after clonidine injection. Mean (Standard Deviation). Unit: mm Hg

Measure	Intrathecal Clonidine n = 10
Change in mean SBP after clonidine injection	79 (28)
Change in DBP after clonidine injection	37 (17)

Population analysed: All subjects met inclusion and exclusionary criteria, and was given an intrathecal injection of clonidine. They were followed for changes in blood pressure for 4 hours.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected during the duration of the study. Some adverse events, such as pregnancy that occurred during the study would have been followed until the delivery of fetus or termination of pregnancy.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Intrathecal Clonidine	0 of 10 (0%)	0 of 10 (0%)	Not reported

Limitations and caveats (from the sponsor): This study was limited by small sample size, and lack of control group.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 4884576Onesti G, Schwartz AB, Kim KE, Swartz C, Brest AN. Pharmacodynamic effects of a new antihypertensive drug, Catapres (ST-155). Circulation. 1969 Feb;39(2):219-28. doi: 10.1161/01.cir.39.2.219. No abstract available.
Background: PubMed 870272Davies DS, Wing AM, Reid JL, Neill DM, Tippett P, Dollery CT. Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine. Clin Pharmacol Ther. 1977 May;21(5):593-601. doi: 10.1002/cpt1977215593.
Background: PubMed 6734692Frisk-Holmberg M, Paalzow L, Wibell L. Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension. Demonstration of a therapeutic window in man. Eur J Clin Pharmacol. 1984;26(3):309-13. doi: 10.1007/BF00548760.
Background: PubMed 321174Reid JL, Wing LM, Mathias CJ, Frankel HL, Neill E. The central hypotensive effect of clonidine. Studies in tetraplegic subjects. Clin Pharmacol Ther. 1977 Apr;21(4):375-81. doi: 10.1002/cpt1977214375.
Background: PubMed 2414580Brown MJ, Struthers AD, di Silvio L. Peripheral alpha 2 adrenoceptor stimulation contributes to the sympatholytic effect of guanfacine in humans. J Cardiovasc Pharmacol. 1985;7 Suppl 6:S159-61. doi: 10.1097/00005344-198500076-00027.
Background: PubMed 6630584Guthrie GP Jr, Kotchen TA. Effects of prazosin and clonidine on sympathetic and baroreflex function in patients with essential hypertension. J Clin Pharmacol. 1983 Aug-Sep;23(8-9):348-54. doi: 10.1002/j.1552-4604.1983.tb02747.x.
Background: PubMed 2455165Mohanty PK, Sowers JR, McNamara C, Thames MD. Reflex vasoconstrictor responses to cardiopulmonary baroreceptor unloading, head-up tilt, and cold pressor testing in elderly mild-to-moderate hypertensives: effect of clonidine. J Cardiovasc Pharmacol. 1987;10 Suppl 12:S135-7.
Background: PubMed 1443738Muzi M, Goff DR, Kampine JP, Roerig DL, Ebert TJ. Clonidine reduces sympathetic activity but maintains baroreflex responses in normotensive humans. Anesthesiology. 1992 Nov;77(5):864-71. doi: 10.1097/00000542-199211000-00005.
Background: PubMed 3513726Houston MC. Treatment of hypertensive emergencies and urgencies with oral clonidine loading and titration. A review. Arch Intern Med. 1986 Mar;146(3):586-9.
Background: PubMed 6534750Masotti G, Scarti L, Poggesi L, Bisi G, Gallini C, Neri Serneri GG. Changes in cardiac function after effective treatment of hypertensive emergencies with i.v. clonidine. Eur Heart J. 1984 Dec;5(12):1036-42. doi: 10.1093/oxfordjournals.eurheartj.a061605.
Background: PubMed 632367Niarchos AP. Evaluation of intravenous clonidine in hypertensive emergencies. J Clin Pharmacol. 1978 Apr;18(4):220-8. doi: 10.1002/j.1552-4604.1978.tb01596.x.
Background: PubMed 2580157Magorien RD, Hermiller JB, Unverferth DV, Leier CV. Regional hemodynamic effects of clonidine in congestive heart failure. J Cardiovasc Pharmacol. 1985 Jan-Feb;7(1):91-6. doi: 10.1097/00005344-198501000-00015.
Individual participant dataSharing planned: No. no individual's data will be shared with anyone other than the members of the study staff, and the confidentiality will be maintained in accordance with HIPAA rules.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Richard L. Rauck, MD principal investigator

Owner

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing clonidine in people with Hypertension, run by The Center for Clinical Research, Winston-Salem, NC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Blood Pressure After Intrathecal Injection of Clonidine. (time frame: Baseline, Every 10 Minutes for first hour after clonidine injection, and every 15 minutes after first hour, until 4 hours after clonidine injection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01297335, which also lists 54 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2016.